细胞间黏附分子1（ICAM-1）在大鼠内脏动脉闭塞性休克发病机制中的作用。

Contribution of intercellular adhesion molecule 1 (ICAM-1) to the pathogenesis of splanchnic artery occlusion shock in the rat.

作者信息

Squadrito F, Altavilla D, Canale P, Ioculano M P, Campo G M, Ammendolia L, Squadrito G, Saitta A, Calapai G, Caputi A P

机构信息

Institute of Pharmacology, School of Medicine, University of Messina, Italy.

出版信息

Br J Pharmacol. 1994 Nov;113(3):912-6. doi: 10.1111/j.1476-5381.1994.tb17079.x.

DOI:10.1111/j.1476-5381.1994.tb17079.x

PMID:7858885

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1510450/

Abstract

It has been suggested that leukocytes play a key role in the pathogenesis of splanchnic artery occlusion shock. Intercellular adhesion molecule 1 (ICAM-1) is an adhesion molecule of crucial importance in the phenomenon of leukocyte accumulation. 2. We investigated the involvement of ICAM-1 in the pathogenesis of splanchnic artery occlusion shock. Splanchnic artery occlusion (SAO) shock was induced in anaesthetized rats by clamping splanchnic arteries for 45 min. Sham-operated animals were used as controls. Survival time, serum tumour necrosis factor-alpha (TNF-alpha), white blood cell (WBC) count, mean arterial blood pressure, myeloperoxidase activity (MPO; studied as a quantitative means to assess leukocyte accumulation) and the responsiveness to acetylcholine of aortic rings were investigated. SAO shocked rats had a decreased survival time (90 +/- 9.5 min, while sham-shocked rats survived more than 4 h), reduced mean arterial blood pressure, increased serum levels of TNF-alpha (201 +/- 10 mu ml-1) and MPO activity in the ileum (0.15 +/- 0.03 mu x 10(-3) per g tissue) and in the lung (1.9 +/- 0.8 mu x 10(-3) per g tissue), leukopenia and reduced responsiveness to acetylcholine (ACh, 10 nM-10 microM) of aortic rings. 3. Administration of monoclonal antibody raised against rat ICAM-1 significantly increased survival time (225 +/- 9 min), reduced leukopenia and MPO activity both in the ileum (0.031 +/- 0.003 mu x 10(-3) per g tissue) and in the lung 0.23 +/- 0.03 mu x 10(-3) per g tissue), improved the cardiovascular changes and restored the responsiveness to ACh of aortic rings. 4. Our findings are consistent with an involvement of adhesion mechanisms in vivo in the pathogenesis of SAO shock and suggest that specific adhesion mechanisms, which support leukocyte accumulation,may represent potentially important therapeutic targets in circulatory shock.

摘要

有人提出白细胞在内脏动脉闭塞性休克的发病机制中起关键作用。细胞间黏附分子1（ICAM - 1）是白细胞聚集现象中至关重要的黏附分子。2. 我们研究了ICAM - 1在内脏动脉闭塞性休克发病机制中的作用。通过钳夹内脏动脉45分钟，在麻醉大鼠中诱导内脏动脉闭塞（SAO）休克。假手术动物用作对照。研究了生存时间、血清肿瘤坏死因子 - α（TNF - α）、白细胞（WBC）计数、平均动脉血压、髓过氧化物酶活性（MPO；作为评估白细胞聚集的定量方法进行研究）以及主动脉环对乙酰胆碱的反应性。SAO休克大鼠的生存时间缩短（90±9.5分钟，而假休克大鼠存活超过4小时），平均动脉血压降低，血清TNF - α水平升高（201±10μg/ml），回肠（0.15±0.03μg×10⁻³/g组织）和肺（1.9±0.8μg×10⁻³/g组织）中的MPO活性增加，白细胞减少，主动脉环对乙酰胆碱（ACh，10nM - 10μM）的反应性降低。3. 给予抗大鼠ICAM - 1的单克隆抗体可显著延长生存时间（225±9分钟），减少白细胞减少以及回肠（0.031±0.003μg×10⁻³/g组织）和肺（0.23±0.03μg×10⁻³/g组织）中的MPO活性，改善心血管变化并恢复主动脉环对ACh的反应性。4. 我们的研究结果表明体内黏附机制参与了SAO休克的发病机制，并提示支持白细胞聚集的特定黏附机制可能是循环性休克潜在的重要治疗靶点。